Download SW_QA158_5_Fluorescein_in_RI_or_RRT_July14

Medicines Q&As
UKMi Q&A 158.5
Does the dose of intravenous fluorescein sodium need to be
adjusted in renal impairment or renal replacement therapy?
Prepared by UK Medicines Information (UKMi) pharmacists for NHS healthcare professionals
Before using this Q&A, read the disclaimer at www.ukmi.nhs.uk/activities/medicinesQAs/default.asp
Date prepared: July 2014
Background
Fluorescein sodium is given by intravenous (IV) injection for the examination of the ophthalmic
vasculature by retinal angiography. The usual adult dose is the equivalent of 500mg of fluorescein, as
a solution of fluorescein 10% or 25%, for example 5 mL of a fluorescein 10% solution as an IV
bolus(1,2,3). A 10% solution of fluorescein (as 566mg fluorescein sodium in 5mL) is available as a
licensed product in the UK (3).
Answer
There is little useful data available for patients with renal insufficiency and patients undergoing renal
replacement therapies receiving fluorescein sodium.
Although fluorescein sodium and its metabolites are almost entirely excreted in the urine, there has
not been an increased incidence of adverse effects reported to date in patients with renal insufficiency
(2). Because it is administered as a single dose, accumulation should not be a problem. The half-life
is short; half-lives of fluorescein and fluorescein glucuronide in plasma are approximately 24 and 264
minutes, respectively (2,4). After IV administration, the urine remains slightly fluorescent for 24 to 36
hours. The systemic clearance of fluorescein is essentially complete by 48 to 72 hours after
administration of 500 mg fluorescein. Although a longer excretion rate in patients with renal
impairment is possible, limited experience in renally impaired subjects (glomerular filtration rate below
20 ml/min) suggests that, in general, no dose adjustment is required in patients with renal
insufficiency undergoing retinal angiography with usual doses of fluorescein sodium (2,3,4,). The
Royal College of Ophthalmologists guidelines for the management of age-related macular
degeneration refer to the use of fundus fluorescein angiography (FFA) and note that renal disease is
not a reason to withhold FFA. They advise however that the presence of renal disease should be
recorded in case of any subsequent patient management issues(5).While existing renal disease are
not reasons for withholding angiography, this information may prove useful in terms of subsequent
patient management particularly in the event of an allergic reaction (5).
There are some case reports and observational studies on small numbers of patients, of the use of
fluorescein for retinal angiography in patients with varying degrees of renal impairment; these include
patients on haemodialysis. However, most of these reports do not specify the dose used or mention
dose adjustment (6,7,8,9,10). In a retrospective cohort study, 2.5mL of 10% sodium fluorescein
solution was given IV to 128 diabetic patients with an eGFR <60mL/min per 1.73m2 undergoing
fluorescein angiography to assess retinopathy. There was no significant change in eGFR from
baseline following fluorescein angiography overall, and also in a subgroup analysis by CKD stage;
(90, 28 and 10 patients had stage 3, 4 and 5 CKD respectively)(11). In a prospective cohort study 44
diabetic patients (eGFR not stated) undergoing fluorescein angiography to assess retinopathy
received 500mg sodium fluorescein solution IV. Mean serum creatinine increased from 1.09 mg/dl
(96.3 micromol/L) at baseline to 1.16 mg/dl (102.5 micromol/L) at day 3 after angiography. No
significant adverse effects were observed (12).There is limited evidence however, that fluorescein
may interfere with certain laboratory tests including estimation of serum creatinine (3,13).
Dialysis
The manufacturer of Anatera 100mg/ml recommends reducing the dose to 250mg in dialysed patients
(3).
Available through NICE Evidence Search at www.evidence.nhs.uk
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Medicines Q&As
 Haemodialysis (HD)
Fluorescein sodium is highly protein bound (70-80%) (4), which does not favour removal by HD.
However, it has a low molecular weight (MW) and low volume of distribution (Vd) (0.5 to 0.8L/kg)(4),
which are both characteristics that favour removal by HD. Fluorescein sodium is water-soluble which
would favour removal by an aqueous dialysate.(1,2,14,15) It is therefore difficult to predict how much
could be removed by HD. However due to the short half-life and the fact that it is a single dose,
accumulation should not be a problem in haemodialysis patients.
 Continuous Ambulatory Peritoneal Dialysis (CAPD)
Fluorescein sodium’s low MW and low Vd favour removal by CAPD, but its high protein binding does
not (15). It is therefore difficult to predict how much could be removed by CAPD. However due to the
short half-life and the fact that it is a single dose, accumulation should not be a problem in CAPD
patients.
Continuous arterio-venous or veno-venous haemofiltration/haemodialysis/ haemodiafiltration
 (CAVH/CAVHD/CAVHDF) or (CVVH/CVVHD/CVVHDF)
Fluorescein sodium’s low Vd favours removal by filtration/diafiltration. The filters can remove only
non-protein bound drug and fluorescein sodium is highly protein bound. Its low MW will allow passage
through the large pore size filters but again it is difficult to predict how much removal is likely to take
place (15). Fluorescein sodium’s short half-life and the fact that it is a single dose should mean that
accumulation should not be a problem in patients on filtration/diafiltration.
Summary
Whilst limited data are available, it does not appear that dose adjustments are required in patients
with renal impairment undergoing retinal angiography with usual doses of fluorescein sodium. The
manufacturer recommends reducing the dose to 250mg in dialysed patients.
Limitations
There is little useful data available for patients with renal insufficiency and patients undergoing renal
replacement therapies receiving fluorescein sodium, therefore these recommendations are based on
theoretical considerations.
References
1. Martindale Sweetman S. editor. Martindale: The Complete Drug Reference [online] London:
Pharmaceutical Press http://www.medicinescomplete.com (Accessed on 29/07/14).
2. DRUGDEX System: Fluorescein. Drugdex Drug Evaluations. In: DRUGDEX System (electronic
version). Thomson Micromedex, Greenwood Village, Colorado, USA. Available at
http://www.micromedexsolutions.com/home/dispatch (Accessed on 01/07/14 )
3. Summary of Product Characteristics – Anatera (fluorescein)100mg/ml solution for injection. Alcon
Laboratories Ltd. Accessed via http://www.medicines.org.uk/emc / on 01/07/14 [date of revision of the
text10 July 2013].
4. Data Sheet. FLUORESCITE. Alcon Laboratories (Australia) Pty Ltd Medsafe. New Zealand
Medicines and Medical Devices Safety Authority.
Date of last amendment 02/09/13 http://www.medsafe.govt.nz/searchResults.asp?q=fluorescein
http://www.medsafe.govt.nz/profs/datasheet/f/fluoresciteinj.pdf
accessed on 29.7.14
5. The Royal College of Ophthalmologists. Age-Related Macular Degeneration: Guidelines for
Management September 2013 Accessed via www.rcophth.ac.uk on 29/7/14
6. Lemaitre-Labilloy C et al. Acute choroidal closure caused by hemodialysis accident in an
amyloidosic patient. Graefe’s Arch Clin Exp Ophthalmol 2006; 244: 758-60
7. Taban M et al. Ocular findings in IgA nephropathy with renal failure and hypertension. J Pediatr
Ophthalmol Strabismus 2006;43: 378-80
8. Tokuyama T et al. Effects of haemodialysis on diabetic macular leakage. Br J Ophthalmol 2000; 84:
1397-1400
9. Niutta A et al. Fluoroangiographic findings in hemodialyzed patients. Ann Ophthalmol 1993; 25:
375-80
Available through NICE Evidence Search at www.evidence.nhs.uk
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Medicines Q&As
10.Lafaut BA et al. Fundus fluorescein angiography of patients with severe hypertensive nephropathy.
Graefe’s Arch Clin Exp Ophthalmol 1997; 235: 749-754
11. Kameda Y et al. Renal function following fluorescein angiography in diabetic patients with chronic
kidney disease. Diabetes Care 2009; 32: e31
12. Alemzadeh-Ansari MJ et al. Effect of fluorescein on renal function among diabetic patients.
Nefrologia 2011; 31:612-13
13. Medical Information. Alcon Laboratories Limited. Personal Communication. 23.5.12
14. Dollery C. editor. Therapeutic Drugs 2nd Ed, Edinburgh: Churchill Livingstone; 1999, p. F99
15. Ashley C, Morlidge C, editors. Introduction to Renal Therapeutics, London: Pharmaceutical Press;
2008, p. 133-5
Quality Assurance
Prepared by
Julia Kuczynska, South West Medicines Information and Training, University Hospitals Bristol NHS
Foundation Trust (based on earlier work by Caroline Metters and Richard Cattell)
Date Prepared
29 July 2014
Checked by
Trevor Beswick
South West Medicines Information and Training
Date of check
7 August 2014
Search strategy
Embase :[ *FLUORESCEINexp or *RETINA FLUORESCEIN ANGIOGRAPHYexp] and [*KIDNEY
FAILUREexp or *RENAL REPLACEMENT THERAPYexp]
Medline : [*FLUORESCEIN ANGIOGRAPHYexp or *FLUORESCEINexp] and [*RENAL
INSUFFICIENCYexp or *RENAL REPLACEMENT THERAPYexp]
In-house database: FLUORESCEIN
In-house renal files and specialist texts: FLUORESCEIN
Internet Search (GOOGLE): FLUORESCEIN ANGIOGRAPHY KIDNEY
NHS Evidence :FLUORESCEIN and [KIDNEY or RENAL]
Cochrane Library: FLUORESCEIN and KIDNEY
Manufacturer: Alcon Laboratories Limited. Medical Information (contacted on 23.5.12)
Available through NICE Evidence Search at www.evidence.nhs.uk
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